Liquid chromatographic isolation of vincristine and vinblastine

A fundamentally new method is described for the separation of the dimeric indole alkaloids vincristine and vinblastine from monomeric indole alkaloid impurities. This method uses an RP-18 high-performance liquid chromatography column with a methanol-water mobile phase containing an inorganic acid and an unusually low concentration of inorganic buffer. By keeping the buffer concentration low, the elution of all indole alkaloids is retarded, but the dimeric ones are retarded more than the monomeric ones. A theoretical model developed to explain this behavior postulates that the anions of the buffer solubilize the protonated indole alkaloids by pairing with them. Lowering the buffer concentration reduces the availability of pairing ions and thus decreases the mobile phase affinity of protonated alkaloids, particularly those having a 2+ charge. A similar approach may be applicable in other situations where ionogenic organic compounds having a particular valence must be separated from related compounds having different valences, or from non-ionogenic compounds.     

Solid-phase extraction of vinblastine and vincristine from plasma and urine: variable drug recoveries due to non-reproducible column packings

A sensitive and selective high-performance liquid chromatographic (HPLC) method for the determination of vinblastine and vincristine in plasma and urine is described. The drugs are isolated from 1.0 ml of the biological fluid with a solid-phase extraction column (Bond-Elut Diol). The HPLC method was combined with electrochemical detection at +850 mV versus an Ag/AgCl reference electrode. The detection limit is 100 pg for vinblastine and 250 pg for vincristine with a signal-to-noise ratio of 3, which permits the determination of these compounds in biological fluids at the nanogram level. Evaluation of the isolation method revealed that the drug recoveries and the reproducibility of the extraction procedure depend on the batch number of the solid-phase extraction column used.     

Simultaneous determination of vincristine, vinblastine, catharanthine, and vindoline in leaves of catharanthus roseus by high-performance liquid chromatography

A simple reversed-phase liquid chromatographic method is developed for the simultaneous quantitation of the anticancerous drugs vincristine, vinblastine, and their precursors catharanthine and vindoline using a Merck Chromolith Performance reversed-phase high-performance liquid chromatography column. A better resolution is obtained in comparison with available particulate-type C18 columns. The column provides good reproducibility and peak symmetry. Chromatography is carried isocratically with a mobile phase of acetonitrile-0.1M phosphate buffer containing 0.5% glacial acetic acid (21:79, v/v; pH 3.5) at a flow rate of 1.2 mL/min and UV detection at 254 nm. Parameters such as linearity, limits of quantitation (LOQ) and detection (LOD), precision, accuracy, recovery, and robustness are studied. The method is selective and linear for alkaloid concentration in the range 0.25 microg-25 microg/mL. The LOQ and LOD are 25, 46, 56, and 32 microg/mL and 8, 14, 18, and 10 microg/mL, respectively. The results of accuracy studies are good. Values for coefficient of variation are 2.50, 1.82, 1.33, and 1.13, respectively. The percent recovery of the alkaloids was found to be 96%, 97%, 98%, and 98%, respectively. Peak purity and homogeneity of these compounds in plant extract is studied using a photodiode-array detector. This simple and rapid method of analysis is applied for the determination of these alkaloids in a large number of leaf extracts of Catharanthus roseus..     

Monitoring the production yields of vincristine and vinblastine in Catharanthus roseus from somatic embryogenesis. Semiquantitative determination by flow-injection electrospray ionization mass spectrometry

A semiquantitative determination of two bis-indole antitumor alkaloids, vincristine and vinblastine, has been performed by flow-injection electrospray ionization mass spectrometric analysis of the extracts of Catharanthus roseus. Leaves and flowers of two different phenotypes (pink flower and white flower) obtained from somatic embryogenesis were thus examined and compared with the field-grown mother plant. Different amounts of vincristine and vinblastine were detected depending on the examined samples.     

Structural isomerism of mono- and sesquiterpenoid skeletons

A generator of chemical structures (CONGEN) has been utilized to investigate two aspects of the structural isomerism of mono- and sesquiterpenoid skeletons: (1) the scope of possible isomers under various structural constraints; and (2) the scope of possible isomers based on a mechanistic model which allows interactive exploration of reactions of formation and interconversion. The possibilities, even under severe constraints, are many more than the structural types commonly encountered in natural. These results indicate the potential danger of structural assignment based in part on biogenic grounds.     

Synthesis of novel N-rich polycyclic skeletons based on azoles and pyridines

An efficient method for the synthesis of new polycyclic skeletons: triaza-benzofluorenes and triaza-pentalenonaphthalene from bicyclic privileged structures imidazopyridine and imidazothiazole, respectively, has been described using the Pictet-Spengler cyclization.     

Syntheses and biological evaluation of vinblastine congeners

Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at < 10(-6) M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10(-4) M concentrations. An ID50 range of >10(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.     

On the distribution of trace elements in human skeletons

Instrumental neutron activation analysis and flameless atomic absorption spectrometry have been used to study the occurence and distribution with a maximum of 25 elements in multiple sites of a skeleton and in the iliac crest of 69 ancient human skeletons. To study the distribution of trace elements between the different bone fractions the material of each sampling site was chemically treated to separate the collagen and the mineral from one another. Losses or contamination during the extraction procedure have been controled in detail by balance calculations. The elements can be subdivided into several groups due to the balance calculation and their association with the mineral. The analysis of the skeleton showed that the trace elements are distributed in varying degrees within a bone and throughout the skeleton their variation seems to be related to functional and structural conditions of the sampling site. The element content was observed to be higher at epiphyseal areas of long bones than in the shaft and higher in trabecular than in cortical bones. It was found that the element content of a single bone sample depends largely on the mass ratio spongiosa/compacta at the sampling site. By investigating an ancient population group, information about the “natural levels” and biological variation of trace elements was obtained. The results for F, Pb, Sr, and Zn in particular suggest that these elements could be useful in the study of health problems in man which involves the bone tissue.     

Voltammetric oxidation of vinblastine and related compounds

The indole alkaloids, vinblastine, catharanthine, and vindoline, gave oxidation waves in mixed aqueous/organic media by cyclic, normal-pulse, and differential-pulse voltammetry (d.p.v). Of the systems investigated, d.p.v. at carbon paste anodes in pH 5.6 acetate buffer in ethanol/water (1:1) is recommended for general analytical work; calibration graphs were linear up to about 1 mM, with limits of detection of 4, 20, and 1.5 μM for vinblastine, catharanthine, and vindoline, respectively. Results obtained by cyclic voltammetry as well as by pulse techniques suggest that electron transfer is preceded by deprotonation and followed by additional chemical reactions. Products of the electrode processes form mechanically unstable films on the electrode surface.     

General Discussion on Chemical Modifications

Recent work on the use of wool in heat- and mass-exchange systems is summarized. Improvements in the transfer of water vapor (e.g., between the inlet and outlet ducts of an air conditioner) have been obtained by application of hydrophilic polymers to the surface of wool fibers. Further improvements in water sorption are obtained by inclusion of deliquescent salts. Drip formation does not occur at high humidities, presumably because of the viscous nature of the polymer/water system. Wool is shown to be a more suitable substrate than polyester.     

Li-Mg-N-H体系储氢材料的热力学和动力学调控

Mg（NH₂）₂-2LiH体系储氢材料具有较高的储氢容量和较适宜的热力学性能,并且其吸放氢过程完全可逆,是目前最有望实现大规模应用的固态储氢材料之一。然而,由于该体系在吸放氢过程中具有较高的动力学壁垒,导致其在200℃以上才能实现快速地吸放氢。因此,国际上对该体系储氢材料的研究主要集中在热力学和动力学的调控方面。本文从成分调变、纳米化和掺杂改性等方面,详细综述了Mg（NH₂）₂-2LiH体系储氢材料热力学和动力学调控的研究现状,并提出了其中存在的问题和相应对策,同时指出了将来的研究方向。     

Electrochemical study on interaction of vincristine with tubulin

In Tris (0.005 mol/L)‐NaCl (0.05 mol/L) buffer solution (pH = 7.10), keeping temperature at 37°C, a highly sensitive reduction peak of the antitumor agent was obtained by linear sweep voltammetry. The peak potential is‐1.56 V (vs. SCE). The peak current is proportional to the concentration of vincristine over the range of 2.1 ± 10^?7‐4.2 ± 10^?6 mol/L with the detection limit of 1.0 ± 10^?7 mol/L. The behavior of the binding of vincristine to tubulin was studied. The results showed that the reaction of tubulin dimer with vincristine formed an electrochemically active complex to be 1:2. Its stability constant is 2.5 ± 10¹⁴. The reduction process of the complex is irreversible with adsorptive characteristics.     

长春碱与中心蛋白的结合及其对蛋白聚集性质的影响

通过光谱、等温滴定量热(ITC)以及分子对接等方法研究了八肋游仆虫中心蛋白N-端半分子(N-EoCen)与长春碱(Vin)之间的相互作用以及Vin对N-EoCen聚集性质的影响。结果表明,Vin可以与N-EoCen以摩尔比1∶1结合于N-EoCen的第一个EF-hand的F螺旋与第二个EF-hand的E、F螺旋之间,条件结合常数约为10⁴L/mol。复合物的形成是放热的过程,主要依靠静电作用与疏水作用。N-EoCen与Vin结合后,构象发生变化,α螺旋含量减少,N-EoCen与Tb³⁺结合能力减弱。最终使得N-EoCen的自聚集以及Tb³⁺诱导的聚集减弱。研究结果为蛋白聚集抑制剂的筛选以及相关药物的研发提供了参考和依据。     

Modifications of the computer programme SCOGS

The computer programme SCOGS has been modified to accept and yield all equilibrium constants involving proton transfer, as concentration quotients. Significant savings in operating time are achieved through use of the FORTRAN H compiler.     

Rearrangement of indene skeletons under mild conditions

Isomerization between two isomers of 1,2-disubstituted 3-aminoindenes occurs via the rearrangement of indene frameworks. In contrast to previous rearrangements of indene derivatives, which occur under high-temperature conditions or the irradiation of light, this rearrangement proceeds at room temperature without UV light irradiation. An amino group at the 3-position plays an important role to accelerate the rearrangement under mild conditions.     

Current Status on Plastic Scintillators Modifications

Recent developments of plastic scintillators are reviewed, from 2000 to March 2014, distributed in two different chapters. First chapter deals with the chemical modifications of the polymer backbone, whereas modifications of the fluorescent probe are presented in the second chapter. All examples are provided with the scope of detection of various radiation particles. The main characteristics of these newly created scintillators and their detection properties are given.     

Diels-Alder additions of benzynes within helicene skeletons

Although the contortions required are unprecedented, the benzynes formed by the fluoride-induced elimination of TMSOTf from o-trimethylsilyl [6]- and [7]-helicenol triflates add to another ring of the helicenes rather than to an external furan molecule.     

Synthesis and properties of novel extended BODIPYs with rigid skeletons

Novel extended BODIPYs fused with bicyclo rings were synthesized from bicyclopyrroles by combining Knoevenagel condensation, Suzuki coupling, and O-chelation. The absorption maxima of the BODIPYs ranged from the visible to near-infrared region and the compounds showed good solubility in organic solvents. The solubility of the bicycloBODIPY with 2-naphthyl groups at the α-position of the pyrrole units was particularly high. Heating converted distyrylBODIPY with bicyclo[2.2.2]octene to benzoBODIPY with absorption (748.5?nm) and fluorescence (775.0?nm) in the near-infrared region.